sdLDL

sdLDL

This test is used to refine cardiovascular risk assessment.

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sdLDL

Test Summary

 

sdLDL 

Test Code: 36406

 

Clinical use

  • Assess cardiovascular disease (CVD) risk

Clinical background

Reducing the risk of CVD depends on identifying and managing established risk factors, such as elevated low-density lipoprotein cholesterol (LDL-C). However, not all CVD risk is captured by these risk factors.1 For example, many people hospitalized for coronary artery disease have LDL-C that is not elevated.2 Emerging risk factors may help refine CVD risk assessments, especially among people with borderline (5% to 7.4%) or intermediate (7.5% to 20%) 10-year CVD risk calculated using conventional risk factors.1,3 Improved risk assessment may help identify people who would benefit from more intensive interventions to manage dyslipidemia and lower their risk of CVD.1

Although LDL-C is a well-known risk factor for CVD, LDL is not homogeneous and comprises particles with varying size and atherogenic properties. Of these particles, a subset known as small, dense LDL (sdLDL) is emerging as the most important CVD risk factor.4,5 Because of their biophysical properties, sdLDL particles are more atherogenic than other LDL particles, lipoproteins, and triglycerides.6 Overabundance of sdLDL particles is associated with CVD and is often accompanied by other lipid abnormalities (eg, lowered high-density lipoprotein-C and elevated triglycerides).

The methods used to quantify sdLDL particles are technically challenging and not well-suited for routine clinical applications. However, Quest Diagnostics and the Cleveland HeartLab offer a 1-step enzymatic assay to quantify sdLDL cholesterol (sdLDL-C). This enzymatic assay provides an automated, reproducible readout of sdLDL particle abundance,7,8 which is associated with risk of incident CVD (including coronary heart disease [CHD], heart attack, and stroke). In a meta-analysis of studies comparing high vs low sdLDL, people with high sdLDL had over 1.3-fold higher risk (odds ratio, 1.36; 95% CI, 1.21-1.52) for incident CHD compared to those with low sdLDL.9 Among the offspring of participants in the Framingham Heart Study, elevated sdLDL-C was reported as the best lipid measure of incident CVD risk at 10-year follow-up (hazard ratio, 1.42; 95% CI, 1.21-1.68).6 Furthermore, sdLDL-C is associated with risk of incident CHD regardless of LDL-C levels.10,11 sdLDL-C is also more closely correlated with CHD6 and carotid intima-media thickness (a measure of atherosclerosis) than is LDL-C.12

Individuals suitable for testing

  • Individuals who may benefit from refinement of CVD risk assessment

Method

  • Enzymatic assay
  • Non-sdLDL-C is released by a surfactant and sphingomyelinase and enzymatically degraded.
  • sdLDL-C is then released by a surfactant and quantified by a colorimetric enzymatic reaction.
  • The cutoff value of this test for increased risk (50 mg/dL) was approximated from the 75th percentile values of sdLDL-C from healthy men and women in the Multi-Ethnic Study of Atherosclerosis, similar to the process used by the National Cholesterol Education Program to establish LDL-C cutoff values.13

Interpretive information

An sdLDL-C concentration ≥50 mg/dL indicates an increased risk of CVD relative to concentrations <50 mg/dL. CVD risk may further increase with sdLDL-C concentration.

References

  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
  2. Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157(1):111-117.e112. doi:10.1016/j.ahj.2008.08.010
  3. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/cir.0000000000000678
  4. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002;106(25):3143-3421.
  5. Handelsman Y, Jellinger PS, Guerin CK, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm - 2020 executive summary. Endocr Pract. 2020;26(10):1196-1224. doi:10.4158/cs-2020-0490
  6. Ikezaki H, Lim E, Cupples LA, et al. Small dense low-density lipoprotein cholesterol is the most atherogenic lipoprotein parameter in the prospective Framingham Offspring Study. J Am Heart Assoc. 2021;10(5):e019140. doi:10.1161/jaha.120.019140
  7. Ito Y, Fujimura M, Ohta M, et al. Development of a homogeneous assay for measurement of small dense LDL cholesterol. Clin Chem. 2011;57(1):57-65. doi:10.1373/clinchem.2010.149559
  8. Hirano T, Ito Y, Saegusa H, et al. A novel and simple method for quantification of small, dense LDL. J Lipid Res. 2003;44(11):2193-2201. doi:10.1194/jlr.D300007-JLR200
  9. Liou L, Kaptoge S. Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis. PLoS One. 2020;15(11):e0241993. doi:10.1371/journal.pone.0241993
  10. Hoogeveen RC, Gaubatz JW, Sun W, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2014;34(5):1069-1077. doi:10.1161/ATVBAHA.114.303284
  11. Tsai MY, Steffen BT, Guan W, et al. New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34(1):196-201. doi:10.1161/ATVBAHA.113.302401
  12. Ikezaki H, Furusyo N, Yokota Y, et al. Small dense low-density lipoprotein cholesterol and carotid intimal medial thickness progression. J Atheroscler Thromb. 2020;27(10):1108-1122. doi:10.5551/jat.54130
  13. s LDL-EX "SEIKEN". Package insert. Denka Seiken USA Inc; 2018.

Content reviewed 02/2023

top of page

This test is used to refine cardiovascular risk assessment.

Test Guide List

sdLDL

Test Summary

 

sdLDL 

Test Code: 36406

 

Clinical use

  • Assess cardiovascular disease (CVD) risk

Clinical background

Reducing the risk of CVD depends on identifying and managing established risk factors, such as elevated low-density lipoprotein cholesterol (LDL-C). However, not all CVD risk is captured by these risk factors.1 For example, many people hospitalized for coronary artery disease have LDL-C that is not elevated.2 Emerging risk factors may help refine CVD risk assessments, especially among people with borderline (5% to 7.4%) or intermediate (7.5% to 20%) 10-year CVD risk calculated using conventional risk factors.1,3 Improved risk assessment may help identify people who would benefit from more intensive interventions to manage dyslipidemia and lower their risk of CVD.1

Although LDL-C is a well-known risk factor for CVD, LDL is not homogeneous and comprises particles with varying size and atherogenic properties. Of these particles, a subset known as small, dense LDL (sdLDL) is emerging as the most important CVD risk factor.4,5 Because of their biophysical properties, sdLDL particles are more atherogenic than other LDL particles, lipoproteins, and triglycerides.6 Overabundance of sdLDL particles is associated with CVD and is often accompanied by other lipid abnormalities (eg, lowered high-density lipoprotein-C and elevated triglycerides).

The methods used to quantify sdLDL particles are technically challenging and not well-suited for routine clinical applications. However, Quest Diagnostics and the Cleveland HeartLab offer a 1-step enzymatic assay to quantify sdLDL cholesterol (sdLDL-C). This enzymatic assay provides an automated, reproducible readout of sdLDL particle abundance,7,8 which is associated with risk of incident CVD (including coronary heart disease [CHD], heart attack, and stroke). In a meta-analysis of studies comparing high vs low sdLDL, people with high sdLDL had over 1.3-fold higher risk (odds ratio, 1.36; 95% CI, 1.21-1.52) for incident CHD compared to those with low sdLDL.9 Among the offspring of participants in the Framingham Heart Study, elevated sdLDL-C was reported as the best lipid measure of incident CVD risk at 10-year follow-up (hazard ratio, 1.42; 95% CI, 1.21-1.68).6 Furthermore, sdLDL-C is associated with risk of incident CHD regardless of LDL-C levels.10,11 sdLDL-C is also more closely correlated with CHD6 and carotid intima-media thickness (a measure of atherosclerosis) than is LDL-C.12

Individuals suitable for testing

  • Individuals who may benefit from refinement of CVD risk assessment

Method

  • Enzymatic assay
  • Non-sdLDL-C is released by a surfactant and sphingomyelinase and enzymatically degraded.
  • sdLDL-C is then released by a surfactant and quantified by a colorimetric enzymatic reaction.
  • The cutoff value of this test for increased risk (50 mg/dL) was approximated from the 75th percentile values of sdLDL-C from healthy men and women in the Multi-Ethnic Study of Atherosclerosis, similar to the process used by the National Cholesterol Education Program to establish LDL-C cutoff values.13

Interpretive information

An sdLDL-C concentration ≥50 mg/dL indicates an increased risk of CVD relative to concentrations <50 mg/dL. CVD risk may further increase with sdLDL-C concentration.

References

  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003
  2. Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157(1):111-117.e112. doi:10.1016/j.ahj.2008.08.010
  3. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/cir.0000000000000678
  4. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002;106(25):3143-3421.
  5. Handelsman Y, Jellinger PS, Guerin CK, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm - 2020 executive summary. Endocr Pract. 2020;26(10):1196-1224. doi:10.4158/cs-2020-0490
  6. Ikezaki H, Lim E, Cupples LA, et al. Small dense low-density lipoprotein cholesterol is the most atherogenic lipoprotein parameter in the prospective Framingham Offspring Study. J Am Heart Assoc. 2021;10(5):e019140. doi:10.1161/jaha.120.019140
  7. Ito Y, Fujimura M, Ohta M, et al. Development of a homogeneous assay for measurement of small dense LDL cholesterol. Clin Chem. 2011;57(1):57-65. doi:10.1373/clinchem.2010.149559
  8. Hirano T, Ito Y, Saegusa H, et al. A novel and simple method for quantification of small, dense LDL. J Lipid Res. 2003;44(11):2193-2201. doi:10.1194/jlr.D300007-JLR200
  9. Liou L, Kaptoge S. Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis. PLoS One. 2020;15(11):e0241993. doi:10.1371/journal.pone.0241993
  10. Hoogeveen RC, Gaubatz JW, Sun W, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2014;34(5):1069-1077. doi:10.1161/ATVBAHA.114.303284
  11. Tsai MY, Steffen BT, Guan W, et al. New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34(1):196-201. doi:10.1161/ATVBAHA.113.302401
  12. Ikezaki H, Furusyo N, Yokota Y, et al. Small dense low-density lipoprotein cholesterol and carotid intimal medial thickness progression. J Atheroscler Thromb. 2020;27(10):1108-1122. doi:10.5551/jat.54130
  13. s LDL-EX "SEIKEN". Package insert. Denka Seiken USA Inc; 2018.

Content reviewed 02/2023

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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